Anticoagulation Therapy in Non-device-related Intra-cardiac Thrombus

Heart Failure Clinical Trial

— ARGONAUT  

Official title:

Anticoagulant Regimens Given to Achieve Thrombus Regression and Reduce Clinical Outcomes Among Patients With Non Device-related Intra-cardiac Thrombus: a Randomized Assessment Under Direct Oral Anticoagulant and Vitamin-k Antagonist Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05825573
• Other study ID #: PHRC-N/2020/BL-01
• Status: Recruiting
• Phase: Phase 3
• Start date: May 15, 2023
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Benoit Lattuca
• Phone: 33 4 66 68 31 16
• Email: benoit.lattuca[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Left ventricular thrombus is found in 10 to 25% of patients with impaired left ventricular function following ST-segment elevation myocardial infarction and up to 20% in dilated cardiomyopathy in observational studies. Likewise, the incidence of atrial thrombus among atrial fibrillation patients treated by vitamin K antagonist (VKA) is between 0.25% and 7%. Despite anticoagulant therapy, intra-cardiac thrombus remains a severe complication associated with a high risk of systemic embolism and subsequent mortality but also bleeding events related to the anticoagulation therapy. The class of non-vitamin K antagonist direct oral anticoagulant (DOA) has emerged in the last decades and has systematically surpassed VKA in the different clinical settings by providing at minimum a similar efficacy and a better safety profile. In the absence of randomized study in the specific clinical setting of intracardiac thrombus, international Guidelines recommend, on the basis of expert opinion, the use of VKA for at least 3 to 6 months in case of left ventricular thrombus and there is no specific recommendation for thrombus management from other cardiac localizations. In comparison to VKA, the easier management and the large evidence of better safety of DOA make it an interesting anticoagulant strategy. Data for left ventricule thrombosis treatment are limited and only supported by observational cohorts. However, these recent cohorts have shown promising data in this indication reporting similar thrombus regression following DOA in comparison to VKA and similar ischemic outcomes although no head-to-head comparison would be powered. As a consequence, the multicentric randomized ARGONAUT trial aims to confirm these results and evaluate the impact of DOA compared to VKA on thrombus regression and clinical outcomes among patients with intracardiac thrombus, regardless of the thrombus localization and any underlying heart disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with a non-device related intra-cardiac thrombus (all localizations in the four cavities) diagnosed by echocardiography, cardiac CT-scanner or cardiac magnetic resonance imaging independently of underlying heart disease.
• Anticoagulant naïve patient for at least 3 months
• Patient affiliated to a health insurance program
• Patient that accepted not to participate in other studies involving a study medication until the one-year follow-up visit. Registries and studies not involving a study drug are allowed.
• Patient that signed the consent form

Exclusion Criteria:

• Active internal bleeding or recent (< 6 months) major bleeding event requiring surgical procedure or transfusion
• History of intracranial, intraocular, spinal bleeding or known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months
• Planned invasive procedure with potential for uncontrolled bleeding
• Impaired hemostasis such as known International Normalized Ratio (INR) >1.5; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count <100,000/µL)
• Severe chronic renal failure (creat. clearance<30ml/min)
• Known significant liver disease
• Device related thrombus (mechanical valve prosthesis, left atrial appendage or septal closure devices, pacemaker leads)
• Patients with mechanical valve prosthesis
• Cardiogenic shock
• Pregnancy or breast-feeding patient
• Known allergy or hypersensitivity to VKA or DOA drugs
• Inability or unwillingness to comply with study-related procedures
• Participation in another clinical research protocol with other investigational agents or devices within the previous 30 days, planned use of investigational drugs or devices, or previous enrolment in this trial (participation in a trial of routine care is authorized at the same time)
• Patient under tutorship or curatorship

Related Conditions & MeSH terms

• Heart Failure
• Intracardiac Thrombus
• STEMI
• Thrombosis

Intervention

Drug:
• Vitamin K antagonist
VKA study medications (Warfarin, Fluindione and Acenocoumarol) will be prescribed and supplied in the usual setting of patient care with respect of the international guidelines and recommended dose protocols and will not be specifically supplied for the trial. Anticoagulant treatment will be prescribed for 6 months. The recommended INR target will be [2-3] and [2-2.5] for patients treated with concomitant antiplatelet therapy. Biological monitoring will be performed at discretion of physicians as usual care.
• Direct oral anticoagulant
DOA study medications (Apixaban, Rivaroxaban and Dabigatran) will be prescribed and supplied in the usual setting of patient care and will not be specifically supplied for the trial. The usual doses of DOA will be prescribed: dabigatran 150mg twice a day, apixaban 5mg twice a day and rivaroxaban 20mg once a day. The adjusted doses (dabigatran 110mg twice a day, apixaban 2.5mg twice a day and rivaroxaban 15mg once a day) will be prescribed according to clinical practice treatment guidelines.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	Ch Auxerre	Auxerre
France	Ch Avignon	Avignon
France	CH Bastia	Bastia
France	Hôpital Cardiologique du Haut Lévêque	Bordeaux
France	CHU Brest	Brest
France	CH Chartres	Chartres
France	CHU Gabriel Montpied	Clermont-Ferrand
France	CH Compiègne Noyon	Compiègne
France	Hôpital Privé Dijon Bourgogne	Dijon
France	Groupe Hospitalier Mutualiste	Grenoble
France	CHU Lille	Lille
France	CHU Limoges	Limoges
France	Hôpital Cardiovasculaire Louis Pradel	Lyon
France	AP-HM CHU La Timone	Marseille
France	CHR Metz-Thionville	Metz
France	CHU Arnaud de Villeneuve	Montpellier
France	Clinique du Millenaire	Montpellier
France	CHU Nantes	Nantes
France	CHU Nice	Nice
France	CHU de Nimes	Nîmes
France	AP-HP CHU Bichat	Paris
France	AP-HP CHU Lariboisière	Paris
France	Ap-Hp Hegp	Paris
France	AP-HP Hopital Ambroise Paré	Paris
France	CHU Pitié-Salpêtrière	Paris
France	CH Francois Mitterand	Pau
France	CHU Poitiers	Potiers
France	CHU Rennes	Rennes
France	Centre Cardiologique du Nord	Saint-Denis
France	CHU Strasbourg	Strasbourg
France	CHU Toulouse	Toulouse
France	Centre Hopistalier de Valence	Valence
France	Ch Bretagne Atlantique	Vannes
Réunion	CHU La réunion NORD	Saint-Denis

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Countries where clinical trial is conducted

France,  Réunion, 

References & Publications (1)

Lattuca B, Bouziri N, Kerneis M, Portal JJ, Zhou J, Hauguel-Moreau M, Mameri A, Zeitouni M, Guedeney P, Hammoudi N, Isnard R, Pousset F, Collet JP, Vicaut E, Montalescot G, Silvain J; ACTION Study Group. Antithrombotic Therapy for Patients With Left Ventricular Mural Thrombus. J Am Coll Cardiol. 2020 Apr 14;75(14):1676-1685. doi: 10.1016/j.jacc.2020.01.057. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Net clinical benefit of DOA in comparison to VKA in patients with intra-cardiac thrombus	Composite endpoint of all-cause death, myocardial infarction, stroke, acute peripheral emboli, acute pulmonary embolism, thrombus persistence and clinically relevant bleedings (BARC 2 to 5 bleedings)	6 months
Secondary	All cause death between groups	Any death documented during the follow-up independently of cause of death	6 months
Secondary	All cause death between groups	Any death documented during the follow-up independently of cause of death	12 months
Secondary	Myocardial infarction occurrence between groups	All non-fatal MI, excluding MI type 3, which will be captured separately as death	6 months
Secondary	Myocardial infarction occurrence between groups	All non-fatal MI, excluding MI type 3, which will be captured separately as death	12 months
Secondary	Stroke occurrence between groups	Classified as Transient ischemic attack (TIA), Ischemic Stroke, Haemorrhagic Stroke and Undetermined Stroke	6 months
Secondary	Stroke occurrence between groups	Classified as Transient ischemic attack (TIA), Ischemic Stroke, Haemorrhagic Stroke and Undetermined Stroke	12 months
Secondary	Acute peripheral emboli occurrence between groups	All acute artery occlusion (limb, renal or digestive artery occlusion confirmed by clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing	6 months
Secondary	Acute peripheral emboli occurrence between groups	All acute artery occlusion (limb, renal or digestive artery occlusion confirmed by clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing	12 months
Secondary	Acute pulmonary embolism occurrence between groups	Defined as partial or complete occlusion of pulmonary artery or one of its branch confirmed by consistent clinical history and supported by evidence of embolism from surgical specimens, autopsy, angiography or vascular imaging in accordance to international guidelines	6 months
Secondary	Acute pulmonary embolism occurrence between groups	Defined as partial or complete occlusion of pulmonary artery or one of its branch confirmed by consistent clinical history and supported by evidence of embolism from surgical specimens, autopsy, angiography or vascular imaging in accordance to international guidelines	12 months
Secondary	Thrombus persistence between groups	Defined by cardiac imaging (echocardiography, contrast echocardiography, cardiac CT scan or cardiac MRI) as an increased thrombus dimension, a stable thrombus, or a partial thrombus regression	6 months
Secondary	Thrombus persistence between groups	Defined by cardiac imaging (echocardiography, contrast echocardiography, cardiac CT scan or cardiac MRI) as an increased thrombus dimension, a stable thrombus, or a partial thrombus regression	12 months
Secondary	Clinically relevant bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 2 to 5	6 months
Secondary	Clinically relevant bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 2 to 5	12 months
Secondary	Systemic embolism between groups	defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism	6 months
Secondary	Systemic embolism between groups	defined by the composite of stroke, embolic myocardial infarction, peripheral artery occlusion and acute pulmonary embolism	12 months
Secondary	Cardiovascular death between groups	Any death due to myocardial infarction, ischemic and haemorrhagic stroke, systemic embolism, sudden death, low-output failure, fatal arrhythmia, cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other cardiovascular cause. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided.	6 months
Secondary	Cardiovascular death between groups	Any death due to myocardial infarction, ischemic and haemorrhagic stroke, systemic embolism, sudden death, low-output failure, fatal arrhythmia, cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other cardiovascular cause. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided.	12 months
Secondary	Total thrombus recurrence between groups	Recurrence of thrombus on cardiac imaging control following a total thrombus regression during the follow-up	6 months
Secondary	Total thrombus recurrence between groups	Recurrence of thrombus on cardiac imaging control following a total thrombus regression during the follow-up	12 months
Secondary	Major bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 3 to 5	6 months
Secondary	Major bleedings between groups	International Bleeding Academic Research Consortium (BARC) types 3 to 5	12 months